Vitamin D is essential for life in higher animals. It is one of the important regulators of calcium and phosphorus and is required for proper development and maintenance of bone. However, during the past decade, the spectrum of activities promoted by 1,25-(OH).sub.2 D.sub.3 has been found to extend far beyond a role in calcium homeostasis. In addition to its action on the intestine, bone, kidney, and parathyroid glands to control serum calcium, this hormone has been shown to have important cell differentiating activity. Receptors for this hormone have been identified in dozens of different target cells that respond to 1,25-(OH).sub.2 D.sub.3 with a diverse range of biological action. These newly discovered activities have suggested other therapeutic applications of 1,25-(OH).sub.2 D.sub.3 including hyperparathyroidism, psoriasis, cancer, and immune regulation.
Secondary hyperparathyroidism is a universal complication in patients with chronic renal failure. Because of its ability to suppress parathyroid hormone (PTH), 1,25-(OH).sub.2 D.sub.3 has been used with success in the treatment of secondary hyperparathyroidism, Slatopolsy, et al, "Marked Suppression of Secondary Hyperparathyroidism by Intravenous Administration of 1,25-dihydroxycholecalciferol in Uremic Patients", J. Clin. Invest. 74:2136-2143, 1984. Its use is often precluded, however, by the development of hypercalcemia resulting from its potent action on intestinal absorption and bone mineral mobilization.
Hyperphosphatemia is also a persistent problem in chronic hemodialysis patients and can be further aggravated by therapeutic doses of 1,25-(OH).sub.2 D.sub.3. Delmez et al, "Hyperphosphatemia: Its Consequences and Treatment in Patients with Chronic Renal Disease", Am. J. Kidney Dis. 19:303-317, 1992; Quarles et al, "Prospective Trial of Pulse Oral versus Intravenous Calcitriol Treatment of Hyperparathyroidism in ESRD", Kidney Int. 45:1710-1721,1994. In addition, the control of phosphate absorption with large doses of calcium carbonate, Meyrier et al, "The Influence of a High Calcium Carbonate Intake on Bone Disease in Patients Undergoing Hemodialysis", Kidney Int. 4:146-153, 1973; Moriniere et al, "Substitution of Aluminum Hydroxide by High Doses of Calcium Carbonate in Patients on Chronic Hemodialysis: Disappearance of Hyperaluminaemia and Equal Control of Hyperparathyroidism", Proc. Eur. Dial Transplant Assoc. 19: 784-787, 1983; Slatopolsky et al, "Calcium Carbonate as a Phosphate Binder in Patients with Chronic Renal Failure Undergoing Dialysis", New Engl. J. Med. 315:157-161, 1986, only increases the risk of hypercalcemia from 1,25-(OH).sub.2 D.sub.3 therapy. Thus, an analog of 1,25-(OH).sub.2 D.sub.3 that can suppress PTH with minor effects on calcium and phosphate metabolism would be an ideal tool for the control of secondary hyperparathyroidism.